BBC News says that a “flawed gene” has been linked to ovarian cancer. The website says that, by looking at the DNA of 17,000 women, scientists have identified a genetic flaw that can increase the risk of the cancer. Carrying two copies of the identified gene can apparently increase the risk of cancer by 40%, and around 15% of women carry at least one copy of this gene.
This study has identified several variations in the DNA of chromosome 9 that are associated with risk of ovarian cancer. One particular variation called SNP rs3814113 was most strongly associated with risk of ovarian cancer, with the common variant associated with increased risk. As ovarian cancer has symptoms that can be difficult to interpret, cases are often diagnosed at quite an advanced cancer stage when the chances of recovery have become slim. The identification of common ovarian cancer susceptibility genes may offer the potential to identify which women face the greatest risk of the disease and provide them with earlier treatment. While this work is an important early step towards such a goal, genetic screening for ovarian cancer is still likely to be some way off.
Where did the story come from?
Honglin Song and several colleagues from around the world carried out this research, which was published in the peer-reviewed scientific journal Nature Genetics. The study received financial support from numerous sources, including Cancer Research UK.
What kind of scientific study was this?
This was a genetic study looking for DNA variations associated with ovarian cancer.
The authors say that ovarian cancer is known to have a major inheritable component, but the genes known to be associated with the disease (principally BRCA1 and BRCA2) seem to account for less than half the risk related to hereditary factors. In this genome-wide association study (GWAS) they aimed to identify common ovarian cancer susceptibility alleles (variations within the DNA).
In the first stage of the study the researchers looked at the genetic sequences of DNA in 1,817 ovarian cancer cases, comparing them with 2,353 control subjects without cancer. They specifically looked at about 2.5 million single letter variations in the DNA sequence, called single nucleotide polymorphisms or SNPs, and how these varied between cases and controls.
They then looked for variations that were more or less common in the cases than in the controls.
In the first stage of the study 22,790 SNPs were demonstrated most likely to be associated with ovarian cancer. In the second stage of the study these were examined in a further 4,274 cases and 4,809 controls of European ancestry.
Finally, the researchers combined data from the first and second stages and identified the SNP showing the strongest association in this analysis, known as rs3814113. This was then looked at in 2,670 cancer cases and 4,668 controls who were part of the Ovarian Cancer Association Consortium (OCAC).
What were the results of the study?
From analysis of the first and second stages of the study the researchers identified 12 SNPs that were significantly associated with decreased risk of ovarian cancer. These were all located on the same region of the short arm of chromosome 9, a section known as 9p22. The strongest association seen was in SNP rs3814113. When the researchers looked for its presence in the OCAC sample, the association was further enforced.
Carrying of the less common ‘minor’ allele was associated with an 18% decreased risk of ovarian cancer compared to carrying two copies of the common allele [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.79 to 0.86]. This suggests that carriage of the more common allele is associated with increased risk. Risk of cancer was decreased whether people carried one or two copies of these variants.
The minor allele was detected in about 32% of controls and, on this basis, the particular allele variation was calculated to contribute about 0.7% of the genetic ovarian cancer risk. This suggests there are likely to be multiple genes that each have a small effect.
The association differed by type of ovarian cancer, with the strongest decreased risk being for serous ovarian cancer (OR 0.77, 95% CI 0.73 to 0.81).
What interpretations did the researchers draw from these results?
The authors conclude that they found an association between ovarian cancer risk and variations in chromosome region 9p22.2, most significantly an association with the rs3814113 variation.
The authors say that they have been the first to identify that the common variation confers susceptibility to ovarian cancer, and that understanding the role of genetic susceptibility may help in facilitating disease prevention and developing treatments.
What does the NHS Knowledge Service make of this study?
As ovarian cancer has symptoms that are often difficult to interpret, cases are commonly diagnosed at quite an advanced cancer stage, which can make the chances of recovery slim. The ability to identify women with common susceptibility genes might offer improved options for detection, treatment and, hopefully, longer survival. However, while this work is a promising step forward, options such as genetic screening are likely to be some way in the future.
This study has identified several gene variations of chromosome 9 that are associated with risk of ovarian cancer. While the SNP rs3814113 was most strongly associated with risk of cancer, the SNP does not lie within a gene, so it is unclear whether it is actually causing the risk association or whether it is just close to the actual variant responsible.
Additionally, there are likely to be other variants that have effects on ovarian cancer risk that have not been detected in this study. As the researchers say, resequencing of the 9p22.2 region and further genotyping in ovarian cancer cases and controls will be needed to clarify the likely causal variant(s).
It should also be noted that this study primarily considered ovarian cancer as a single disease, but when they looked at the effects of the SNP related to subtypes of cancer they found that risk associations varied. Hence, different types of ovarian cancer may have different biology, and genetic susceptibility may differ by subtype.
Dr Simon Gayther, an author of the study, is reported in The Guardian as saying, “It is premature to say we are in a position to set up a screening programme at the moment, but in 10 years' time we will be in a position to identify several more of these genetic factors, then you could see screening being offered on a population level. If we could combine a genetic screening programme and a programme to spot early signs of the disease we could save many lives in the future.”